1. Field of the Invention
The present invention relates to fluorescent probes and genetic barcodes and methods for detection and analysis of gene characterization, rearrangement, translocation and expression in cancer.
2. Related Art
Our ageing population and the increasing cost of health care in all parts of the world require innovative solutions in order to be able to continue offering affordable care to all individuals. To contain the cost of care of cancer patients, for example, one approach targets the development and marketing of novel diagnostic technologies that help to stratify patient populations and identify those who would benefit from a particular treatment. This has been documented well in cases of patients with breast cancer, where estrogen and progesterone receptor status (i.e., expression levels) and amplification of growth factor receptor genes are taken into consideration, when therapeutic decisions have to be made.
In the US, the prevalence of breast cancer is roughly 100 per 100,000 (0.1%) females in any given year with a mortality rate of less than 30 per 100,000 females. While the etiology and pathogenesis of breast carcinomas remain unclear, there is overwhelming evidence that the abnormal expression of receptor tyrosine kinase genes due to gene amplification, deletions or changes in the regulation of gene expression may lead to transformation of non-malignant cells and promote tumor dissemination and invasiveness. Overexpression of the Her-2/neu protein (the product of the ErbB2 gene) and amplification of the ErbB2 gene are the most widely accepted prognostic indicator of aggressive malignant behavior of invasive breast carcinoma. Accurate detection of Her-2/neu overexpression is critical in identifying patients suitable for serotherapy with humanized monoclonal antibody (Herceptin). Fluorescence in situ hybridization (FISH) has been found to be more accurate than immunohistochemical staining using antibodies against the Her-2/neu protein.
Overexpression of another receptor tk gene, the epidermal growth factor receptor (EGFR, ERBB1) has also been shown to parallel progression to a more malignant phenotype in breast and other cancers. No diagnostic assays that allow an accurate detection of rearrangements while scoring of the number of copies of the EErbB 1 and ErbB2 genes are presently available.
In the area of Her-2/positive breast cancer, Dako's HercepTest currently leads the market. Competitors include Oncor's Inform Her-2/neu gene detection system, Vysis/Abbott PathVision's Her-2 DNA probe kits, and possibly Monogram's dimerization assay. Oncor and PathVision's products are based on fluorescence in situ hybridization detection of the Her-2/neu gene. Both tests, along with Dako's product, have been approved by the FDA.
The ErbB1 gene, coding for the epidermal growth factor-1 protein, is also know to be amplified in a subset of breast carcinomas, where is alters the cells' response to external factors among them therapeutic agents. Yet, no assay exists to test cells in a single experiment for alterations of both, ErbB1 and ErbB2, abnormalities.